Human immunodeficiency virus (HIV) is the causative agent of acquired immune deficiency syndrome (AIDS), which is characterized by immune suppression resulting from selective infection and death of T lymphocytes (Sarin, P., Ann. Rev. Pharmacol. 28:411-428 (1988)). Clinical manifestations of the disease include severe immune deficiency, which is generally accompanied by malignancies and opportunistic infections. According to current estimates from the World Health Organization, 1 in 250 people are infected with HIV worldwide.
Due to the devastating effects of the virus and the high mortality rate among HIV-infected individuals, much effort, time and money have been expended in the attempt to develop methods for preventing HIV infection (prophylactic methods) and for treating already infected individuals (therapeutic methods). However, only limited progress has been made to date.
The potential efficacy of a HIV vaccine is suggested by studies in the simian AIDS model system. Vaccines composed of whole, inactivated virions of simian immunodeficiency virus (SIV) were found to confer at least partial protection against challenge with either live virus or cell-associated virus (Langlois, A. J., et al., Science 255:292-293 (1992); Le Grand, R., et al., Nature 355:684 (1992); Osterhaus, A., and P. De Vries, ibid., pp. 684-685; Cranage, M. P., et al., ibid., pp. 685-686). It has been observed that "whole, inactivated SIV preparations induce the strongest and most consistent protection thus far experienced in experimental animal studies" (Langlois, 1992 supra).
A major problem in obtaining whole, inactivated HIV vaccines, however, has been presented by the tradeoff between safety and immunogenicity. Killed HIV currently used in human immunotherapy trials is required to be prepared through two independent inactivation protocols, each of which must be adequate to completely inactivate the virus on its own. The physical and chemical inactivation treatments currently used have resulted in some loss of immunogenicity of the vaccine due to partial destruction of the virions. A method which leaves the virion structure intact, yet which renders the virions completely noninfectious, would be a significant improvement in vaccine development.
Besides vaccines, drugs which inhibit various stages of HIV infection of T cells and the HIV life cycle in infected cells have been suggested as another approach in the development of therapies against HIV infection. A considerable amount of information is available on viral entry, reverse transcription of the RNA genome, and expression of viral gene products. In contrast, little is known about packaging of the viral genome, assembly of the virion, and budding of the mature virion from the infected cell. One hindrance to HIV research and drug development is the risk of infection to researchers working with reagents which are contaminated with or derived from live HIV. Thus, a means to produce HIV reagents which are totally noninfectious would relieve some of the cost, in terms of risks to workers, and necessary equipment and facilities, of drug development and HIV research.